Oligomerized Amyloid-<i>β</i><sub>1-40</sub> Peptide Favors Cholesterol, Oxysterol, and Fatty Acid Accumulation in Human Neuronal SK-N-BE Cells — Oak Academic Publishing
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Oligomerized Amyloid-<i>β</i><sub>1-40</sub> Peptide Favors Cholesterol, Oxysterol, and Fatty Acid Accumulation in Human Neuronal SK-N-BE Cells
Laboratoire de Biochimie (LR12ES05)-Lab-NAFS “Nutrition, Aliments Fonctionnels et Santé Vasculaire”, Faculté de Médecine, Université de Monastir, Monastir, Tunisie
,
Equipe “Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique” (EA 7270), Université de Bourgogne-Franche Comté/INSERM, Dijon, France
,
Laboratoire de Biochimie (LR12ES05)-Lab-NAFS “Nutrition, Aliments Fonctionnels et Santé Vasculaire”, Faculté de Médecine, Université de Monastir, Monastir, Tunisie
,
Equipe “Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique” (EA 7270), Université de Bourgogne-Franche Comté/INSERM, Dijon, France
1 Laboratoire de Biochimie (LR12ES05)-Lab-NAFS “Nutrition, Aliments Fonctionnels et Santé Vasculaire”, Faculté de Médecine, Université de Monastir, Monastir, Tunisie
2 Equipe “Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique” (EA 7270), Université de Bourgogne-Franche Comté/INSERM, Dijon, France
3 Laboratoire de Biochimie (LR12ES05)-Lab-NAFS “Nutrition, Aliments Fonctionnels et Santé Vasculaire”, Faculté de Médecine, Université de Monastir, Monastir, Tunisie
4 Equipe “Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique” (EA 7270), Université de Bourgogne-Franche Comté/INSERM, Dijon, France
Amyloid peptide, the main component of senile plaques, is a major biological characteristic of Alzheimer’s disease (AD). The aim of the present study conducted on human neuronal SK-N-BE cells was to evaluate whether oligomerized A β 1-40 -induced cell damages was associated with lipid modifications. Under treatment with A β 1-40 (10 - 100 μM; 24 - 48 h), cell viability was recorded with the MTT test and by measuring LDH activity. Mitochondrial transmembrane potential and ATP production were assessed using flow cytometry and a luciferase-based ATP bioluminescence assay, respectively. Annexin V-CF647 staining assay for cell apoptosis detection was performed using flow cytometry. Potentially intracellular cytotoxic lipids (oxysterols: 7 α -hydroxycholesterol (7 α -OHC), 7 β -hydroxycholesterol (7 β -OHC), and 7-ketocholesterol (7KC), 24(S)-hydroxycholesterol; arachidonic acid (C20:4 n-6); VLCFAs (C22:0, C24:0, C24:6 and C26:0)) were measured using gas chromatography coupled with mass spectrometry. The cellular level of docosahexaenoic acid (C22:6 n-3), often altered in AD, was also quantified. In the presence of A β 1-40 , the percentage of MTT-positive cells decreased and was associated with an increase in LDH activity. In addition, treatment with oligomerized A β 1-40 induced a decrease of mitochondrial transmembrane potential as well as an apoptotic cell death. Sterol analysis revealed a higher cholesterol level and a significant increase of cytotoxic oxysterols per cell (7KC + 7 β -OHC), and of the [(7 β -OHC + 7KC)/cholesterol] ratio, considered as a lipid peroxidation index, in A β 1-40 -treated cells. An enhancement of C20:4 n-6, C22:6 n-3 and saturated VLCFAs was also observed. Therefore, A β 1-40 -induced side effects are associated with intracellular accumulation of lipids, especially cholesterol, oxysterols (7 β -OHC, 7KC), C20:4 n-6, and saturated VLCFAs, which could in turn contribute to neurotoxicity.
Selkoe, D. (1994) Alzheimer’s Disease: A Central Role for Amyloid. Journal of Neuropathology & Experimental Neurology, 53, 438-447. http://dx.doi.org/10.1097/00005072-199409000-00003
Haass, C., Schlossmacher, M.G., Hung, A.Y., Vigo-Pelfrey, C., Mellon, A., Ostaszewski, B.L., Lieberburg, I., Koo, E.H., Schenk, D., Teplow, D.B. and Selkoe, D.J. (1992) Amyloid Beta-Peptide Is Produced by Cultured Cells during Normal Metabolism. Nature, 359, 322-325. http://dx.doi.org/10.1038/359322a0
Bjõrkhem, I. (2006) Crossing the Barrier: Oxysterols as Cholesterol Transporters and Metabolic Modulators in the Brain. Journal of Internal Medicine, 260, 493-508. http://dx.doi.org/10.1111/j.1365-2796.2006.01725.x
Grimm, M.O., Zimmer, V.C., Lehmann, J., Grimm, H.S. and Hartmann, T. (2013) The Impact of Cholesterol, DHA, and Sphingolipids on Alzheimer’s Disease. BioMed Research International, 814390.
Grziwa, B., Grimm, M.O., Masters, C.L., Beyreuther, K., Hartmann, T. and Lichtenthaler, S.F. (2003) The Transmembrane Domain of the Amyloid Precursor Protein in Microsomal Membranes Is on Both Sides Shorter than Predicted. The Journal of Biological Chemistry, 278, 6803-6808. http://dx.doi.org/10.1074/jbc.M210047200
Leoni, V. and Caccia, C. (2013) 24S-Hydroxycholesterol in Plasma: A Marker of Cholesterol Turnover in Neurodegenerative Diseases. Biochimie, 95, 595-612. http://dx.doi.org/10.1016/j.biochi.2012.09.025
Wood, W.G., Li, L., Müller, W.E. and Eckert, G.P. (2014) Cholesterol as a Causative Factor in Alzheimer’s Disease: A Debatable Hypothesis. Journal of Neurochemistry, 129, 559-572. http://dx.doi.org/10.1111/jnc.12637
Seripa, D., D’Onofrio, G., Panza, F., Cascavilla, L., Masullo, C. and Pilotto, A. (2001) The Genetics of the Human APOE Polymorphism. Rejuvenation Research, 14, 491-500. http://dx.doi.org/10.1089/rej.2011.1169
Iuliano, L. (2011) Pathways of Cholesterol Oxidation via Non-Enzymatic Mechanisms. Chemistry and Physics of Lipids, 164, 457-468. http://dx.doi.org/10.1016/j.chemphyslip.2011.06.006
Vaya, J. and Schipper, H.M. (2007) Oxysterols, Cholesterol Homeostasis, and Alzheimer Disease. Journal of Neurochemistry, 102, 1727-1737. http://dx.doi.org/10.1111/j.1471-4159.2007.04689.x
Gamba, P., Guglielmotto, M., Testa, G., Monteleone, D., Zerbinati, C., Gargiulo, S., Biasi, F., Iuliano, L., Giaccone, G., Mauro, A., Poli, G., Tamagno, E. and Leonarduzzi, G. (2014) Up-Regulation of β-Amyloidogenesis in Neuron-Like Human Cells by Both 24- and 27-Hydroxycholesterol: Protective Effect of N-Acetyl-Cysteine. Aging Cell, 13, 561-572. http://dx.doi.org/10.1111/acel.12206
Cholesterol
Oxysterols
Very Long Chain Fatty Acids
Lütjohann, D., Papassotiropoulos, A., Bjõrkhem, I., Locatelli, S., Bagli, M., Oehring, R.D., Schlegel, U., Jessen, F., Rao, M.L., von Bergmann, K. and Heun, R. (2000) Plasma 24S-Hydroxycholesterol (Cerebrosterol) Is Increased in Alzheimer and Vascular Demented Patients. Journal of Lipid Research, 41, 195-198.
Solomon, A., Leoni, V., Kivipelto, M., Besga, A., Oksengard, A., Julin, P., Svensson, L., Wahlund, L., Andreasen, N., Winblad, B., Soininen, H. and Bjorkhem, I. (2009) Plasma Levels of 24S-Hydroxycholesterol Reflect Brain Volumes in Patients without Objective Cognitive Impairments but Not with Alzheimer’s Disease. Neuroscience Letters, 462, 89-93. http://dx.doi.org/10.1016/j.neulet.2009.06.073
Zarrouk, A., Vejux, A., Mackrill, J., O’Callaghan, Y., Hammami, M., O’Brien, N. and Lizard, G. (2014) Involvement of Oxysterols in Age-Related Diseases and Ageing Processes. Ageing Research Reviews, 18, 148-162. http://dx.doi.org/10.1016/j.arr.2014.09.006
Urano, Y., Ochiai, S. and Noguchi, N. (2013) Suppression of Amyloid-β Production by 24S-Hydroxycholesterol via Inhibition of Intracellular Amyloid Precursor Protein Trafficking. The FASEB Journal, 27, 4305-4315. http://dx.doi.org/10.1096/fj.13-231456
Prasanthi, J.R., Huls, A., Thomasson, S., Thompson, A., Schommer, E. and Ghribi, O. (2009) Differential Effects of 24-Hydroxycholesterol and 27-Hydroxycholesterol on Beta-Amyloid Precursor Protein Levels and Processing in Human Neuroblastoma SH-SY5Y Cells. Molecular Neurodegeneration, 4, 1. http://dx.doi.org/10.1186/1750-1326-4-1
Kou, J., Kovacs, G.G., Hoftberger, R., Kulik, W., Brodde, A., Forss-Petter, S., Hõnigschnabl, S., Gleiss, A., Brügger, B., Wanders, R., Just, W., Budka, H., Jungwirth, S., Fischer, P. and Berger, J. (2011) Peroxisomal Alterations in Alzheimer’s Disease. Acta Neuropathologica, 122, 271-283. http://dx.doi.org/10.1007/s00401-011-0836-9
Zarrouk, A., Riedinger, J.M., Ahmed, S.H., Hammami, S., Chaabane, W., Debbabi, M., Ben Ammou, S., Rouaud, O., Frih, M., Lizard, G. and Hammami, M. (2015) Fatty Acid Profiles in Demented Patients: Identification of Hexacosanoic Acid (C26:0) as a Blood Lipid Biomarker of Dementia. Journal of Alzheimer’s Disease, 44, 1349-1359.
Lizard, G., Rouaud, O., Demarquoy, J., Cherkaoui-Malki, M. and Iuliano, L. (2012) Potential Roles of Peroxisomes in Alzheimer’s Disease and in Dementia of the Alzheimer’s Type. Journal of Alzheimer’s Disease, 29, 241-254.
Wang, X., Wang, W., Li, L., Perry, G., Lee, H.G. and Zhu, X. (2014) Oxidative Stress and Mitochondrial Dysfunction in Alzheimer’s Disease. Biochimica et Biophysica Acta, 1842, 1240-1247. http://dx.doi.org/10.1016/j.bbadis.2013.10.015
Zarrouk, A., Vejux, A., Nury, T., El Hajj, H.I., Haddad, M., Cherkaoui-Malki, M., Riedinger, J.M., Hammami, M. and Lizard, G. (2012) Induction of Mitochondrial Changes Associated with Oxidative Stress on Very Long Chain Fatty Acids (C22:0, C24:0, or C26:0)-Treated Human Neuronal Cells (SK-NB-E). Oxidative Medicine and Cellular Longevity, 2012, Article ID: 623257. http://dx.doi.org/10.1155/2012/623257
Pikuleva, I.A. (2006) Cholesterol-Metabolizing Cytochromes P450. Drug Metabolism and Disposition, 34, 513-520. http://dx.doi.org/10.1124/dmd.105.008789
Smith, L.L. (1996) Review of Progress in Sterol Oxidations 1987-1995. Lipids, 3, 453-487. http://dx.doi.org/10.1007/BF02522641
Ferrera, P., Mercado-Gómez, O., Silva-Aguilar, M., Valverde, M. and Arias, C. (2008) Cholesterol Potentiates Beta-Amyloid-Induced Toxicity in Human Neuroblastoma Cells: Involvement of Oxidative Stress. Neurochemical Research, 33, 1509-1517. http://dx.doi.org/10.1007/s11064-008-9623-y
García-Escudero, V., Martín-Maestro, P., Perry, G. and Avila, J. (2013) Deconstructing Mitochondrial Dysfunction in Alzheimer Disease. Oxidative Medicine and Cellular Longevity, 2013, Article ID: 162152. http://dx.doi.org/10.1155/2013/162152
Jiang, F., Mao, Y., Liu, H., Xu, P., Zhang, L., Qian, X. and Sun, X. (2015) Magnesium Lithospermate B Protects Neurons against Amyloid β (1-42)-Induced Neurotoxicity through the NF-κB Pathway. Neurochemical Research, 40, 1954-1965. http://dx.doi.org/10.1007/s11064-015-1691-1
Volonté, C., Amadio, S., Cavaliere, F., D’Ambrosi, N., Vacca, F. and Bernardi, G. (2003) Extracellular ATP and Neurodegeneration. Current Drug Targets—CNS and Neurological Disorders, 2, 403-412. http://dx.doi.org/10.2174/1568007033482643
Barbero-Camps, E., Fernández, A., Baulies, A., Martinez, L., Fernández-Checa, J.C. and Colell, A. (2014) Endoplasmic Reticulum Stress Mediates Amyloid β Neurotoxicity via Mitochondrial Cholesterol Trafficking. American Journal of Pathology, 184, 2066-2081. http://dx.doi.org/10.1016/j.ajpath.2014.03.014
Galbete, J.L., Martin, T.R., Peressini, E., Modena, P., Bianchi, R. and Forloni, G. (2000) Cholesterol Decreases Secretion of the Secreted form of Amyloid Precursor Protein by Interfering with Glycosylation in the Protein Secretory Pathway. Biochemical Journal, 348, 307-313. http://dx.doi.org/10.1042/bj3480307
Refolo, L.M., Malester, B., La Francois, J., Bryant-Thomas, T., Wang, R., Tint, G.S., Sambamurti, K., Duff, K. and Pappolla, M.A. (2000) Hypercholesterolemia Accelerates the Alzheimer’s Amyloid Pathology in a Transgenic Mouse Model. Neurobiology of Disease, 7, 321-331. http://dx.doi.org/10.1006/nbdi.2000.0304
Colell, A., Fernández, A. and Fernández-Checa, J.C. (2009) Mitochondria, Cholesterol and Amyloid Beta Peptide: A Dangerous Trio in Alzheimer Disease. Journal of Bioenergetics and Biomembranes, 41, 417-423. http://dx.doi.org/10.1007/s10863-009-9242-6
Cutler, R.G., Kelly, J., Storie, K., Pedersen, W.A., Tammara, A., Hatanpaa, K., Troncoso, J.C. and Mattson, M.P. (2004) Involvement of Oxidative Stress-Induced Abnormalities in Ceramide and Cholesterol Metabolism in Brain Aging and Alzheimer’s Disease. Proceedings of the National Academy of Sciences of the United States of America, 101, 2070-2075. http://dx.doi.org/10.1073/pnas.0305799101
Zarrouk, A., Nury, T., Samadi, M., O’Callaghan, Y., Hammami, M., O’Brien, N.M., Lizard, G. and Mackrill, J.J. (2015) Effects of Cholesterol Oxides on Cell Death Induction and Calcium Increase in Human Neuronal Cells (SK-N-BE) and Evaluation of the Protective Effects of Docosahexaenoic Acid (DHA; C22:6 n-3). Steroids, 99, 238-247. http://dx.doi.org/10.1016/j.steroids.2015.01.018
Prasad, K.N., Hovland, A.R., La Rosa, F.G. and Hovland, P.G. (1998) Prostaglandins as Putative Neurotoxins in Alzheimer’s Disease. Proceedings of the Society for Experimental Biology and Medicine, 219, 120-125. http://dx.doi.org/10.3181/00379727-219-44323
Bazan, N.G. (2009) Cellular and Molecular Events Mediated by Docosahexaenoic Acid-Derived Neuroprotectin D1 Signaling in Photoreceptor Cell Survival and Brain Protection. Prostaglandins, Leukotrienes and Essential Fatty Acids, 81, 205-211. http://dx.doi.org/10.1016/j.plefa.2009.05.024
Fattahi, M.J. and Mirshafiey, A. (2014) Positive and Negative Effects of Prostaglandins in Alzheimer’s Disease. Psychiatry and Clinical Neurosciences, 68, 50-60. http://dx.doi.org/10.1111/pcn.12092